The growth and differentiation of target tissue can be influenced by trophic agents and extracellular matrix (ECM) components. A series of studies are planned to investigate the role of ECM in regeneration in vivo of muscle, nerve, limb, and taste buds. Antibodies to the ECM macromolecules fibronectin, laminin, and type IV collagen were used to monitor changes in ECM by an indirect immlunofluorescent technique. We were particularly interested in changes in basement membrane (BM) since this structure is thought to act as a tube within which muscle and nerve fiber regeneration occurs. We found that the BM myofibers and Schwann cells was sequentially degraded of its components. Fibronectin was lost first; laminin and type IV collagen disappeared later but at about same time. Although it is known from anatomical studies that BM is degraded, our results demonstrated a biochemical sequence. It is conceivable that the sequential degradation of BM is a signal for myosatellite and Schwann cell proliferation which prepares muscle and nerve for regeneration. In a study of limb regeneration, fibronectin was examined since this ECM glycoprotein is involved in cell-to-cell adhesion, cell-to-substratum binding, and cell migration. After limb amputation in newts, increased amounts of fibronectin appeared throughout the ECM of th undifferentiated blastemal cells and persisted during blastemal growth and early stages of redifferentiation of limb tissues (e.g., cartilage, muscle). As limb tissue matured, most of the ECM fibronectin disappeared. These results showed that fibronectin changed in ECM during the dedifferentiation and redifferentiation of tissues in regenerating newt limb. Our goals are to determine the specific role of ECM components in regeneration and to use this knowledge to promote tissue repair.